Abstract
Mitochondrial inner membrane folds into cristae, which significantly increase its surface and are important for mitochondrial function. The stability of cristae depends on the mitochondrial contact site (MICOS) complex. In human mitochondria, the inner membrane MICOS complex interacts with the outer membrane sorting and assembly machinery (SAM) complex, to form the mitochondrial intermembrane space bridging complex (MIB). We have created knockdown cell lines of most of the MICOS and MIB components and have used them to study the importance of the individual subunits for the cristae formation and complex stability. We show that the most important subunits of the MIB complex in human mitochondria are Mic60/Mitofilin, Mic19/CHCHD3 and an outer membrane component Sam50. We provide additional proof that ApoO indeed is a subunit of the MICOS and MIB complexes and propose the name Mic23 for this protein. According to our results, Mic25/CHCHD6, Mic27/ApoOL and Mic23/ApoO appear to be periphery subunits of the MICOS complex, because their depletion does not affect cristae morphology or stability of other components.
Highlights
Mitochondria are organelles crucial for a number of cellular functions, such as production of energy by oxidative phosphorylation, cellular metabolism, signaling and apoptosis [1]
We conclude that Mic23/apolipoprotein O (ApoO) is a mitochondrial protein and that expression of Sam50 and Mic19/ CHCHD3 has a deleterious effect on mitochondrial membrane potential
To further address Mic23/ApoO as a potential novel subunit of the mitochondrial contact site (MICOS) complex, we have developed an in vitro import assay into isolated mitochondria for the radiolabelled precursor of Mic23/ApoO (Fig. 5A)
Summary
Mitochondria are organelles crucial for a number of cellular functions, such as production of energy by oxidative phosphorylation, cellular metabolism, signaling and apoptosis [1]. Reflecting their endosymbiotic origin, mitochondria possess two membranes that divide them into four subcompartments, outer membrane (OMM), intermembrane space (IMS), inner membrane (IMM) and matrix. The majority of mitochondrial proteins are nuclear-encoded, produced on cytosolic ribosomes and imported into mitochondria with the help of import machineries in mitochondrial membranes. The OMM of mitochondria hosts the translocase of the outer membrane (TOM) complex, which is the main entry point for the majority of mitochondrial proteins. Depending on the PLOS ONE | DOI:10.1371/journal.pone.0120213. Depending on the PLOS ONE | DOI:10.1371/journal.pone.0120213 March 17, 2015
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